PMID- 7713945
OWN - NLM
STAT- MEDLINE
DCOM- 19950515
LR  - 20220318
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 270
IP  - 14
DP  - 1995 Apr 7
TI  - Inhibitory effect of a conjugate between human urokinase and urinary trypsin 
      inhibitor on tumor cell invasion in vitro.
PG  - 8361-6
AB  - Proteolytic enzymes such as urokinase-type plasminogen activator (uPA), plasmin, 
      and collagenase mediate proteolysis by a variety of tumor cells. uPA secreted by 
      tumor cells can be bound to a cell surface receptor via a growth factor-like 
      domain within the amino-terminal fragment (ATF) of the uPA molecule with high 
      affinity. Urinary trypsin inhibitor (UTI) efficiently inhibits the soluble and 
      the tumor cell-surface receptor-bound plasmin and subsequently reduces tumor cell 
      invasion and the formation of metastasis. The anti-invasive effect is dependent 
      on the anti-plasmin activity of the UTI molecule, domain II in particular. We 
      synthesized a conjugate between ATF of human uPA and a native UTI molecule or 
      domain II of UTI (HI-8). The effect of the conjugates (ATF.UTI or ATF.HI-8) on 
      tumor cell invasion in vitro was investigated. ATF.UTI and ATF.HI-8 bound to U937 
      cells in a rapid, saturable, dose-dependent, and reversible manner. A large part 
      of receptor-bound ATF-UTI and ATF.HI-8 remains on the cell surface for at least 5 
      h at 37 degrees C. Inhibition of tumor cell-surface receptor-bound plasmin by 
      ATF.UTI and ATF.HI-8 was markedly enhanced when compared with tumor cells treated 
      either with ATF, UTI, or HI-8. Results of a cell invasion assay showed that 
      ATF.UTI and ATF.HI-8 is very effective at targeting HI-8 specifically to uPA 
      receptor-expressing tumor cells, whereas tumor cells devoid of uPA receptor may 
      be less affected by the conjugates. Our results indicate that cell surface uPA 
      and plasmin activity is essential to the invasive process and that the conjugates 
      exhibit plasmin inhibition to the close environment of the cell surface and 
      subsequently inhibit the tumor cell invasion through Matrigel in an in vitro 
      invasion assay.
FAU - Kobayashi, H
AU  - Kobayashi H
AD  - Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, 
      Shizuoka, Japan.
FAU - Gotoh, J
AU  - Gotoh J
FAU - Hirashima, Y
AU  - Hirashima Y
FAU - Fujie, M
AU  - Fujie M
FAU - Sugino, D
AU  - Sugino D
FAU - Terao, T
AU  - Terao T
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Glycoproteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Trypsin Inhibitors)
RN  - EC 3.4.21.36 (Pancreatic Elastase)
RN  - EC 3.4.21.37 (Leukocyte Elastase)
RN  - EC 3.4.21.7 (Fibrinolysin)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
RN  - OR3S9IF86U (urinastatin)
SB  - IM
MH  - Amino Acid Sequence
MH  - Dose-Response Relationship, Drug
MH  - Fibrinolysin/antagonists & inhibitors
MH  - Glycoproteins/metabolism/*pharmacology
MH  - Humans
MH  - Leukocyte Elastase
MH  - Molecular Sequence Data
MH  - *Neoplasm Invasiveness
MH  - Pancreatic Elastase/antagonists & inhibitors
MH  - Receptors, Cell Surface/metabolism
MH  - Trypsin Inhibitors/metabolism/*pharmacology
MH  - Tumor Cells, Cultured
MH  - Urokinase-Type Plasminogen Activator/metabolism/*pharmacology
EDAT- 1995/04/07 00:00
MHDA- 1995/04/07 00:01
CRDT- 1995/04/07 00:00
PHST- 1995/04/07 00:00 [pubmed]
PHST- 1995/04/07 00:01 [medline]
PHST- 1995/04/07 00:00 [entrez]
AID - S0021-9258(18)94696-X [pii]
AID - 10.1074/jbc.270.14.8361 [doi]
PST - ppublish
SO  - J Biol Chem. 1995 Apr 7;270(14):8361-6. doi: 10.1074/jbc.270.14.8361.